Albumin for Management of Hypervolemic Hyponatremia (AlbuCAT) (AlbuCAT)

Albumin for Management of Hypervolemic Hyponatremia in Patients With Decompensated Cirrhosis. A Proof of Concept Study.

resolution of hyponatremia, defined as an increase in serum sodium of more than 5 mEq/L with a final value > 130 mEq/L, maintained for at least 48 consecutive hours during the 10-day treatment period

Study Overview

• Status: Unknown
• Conditions: Cirrhosis, Liver; Hyponatremia With Excess Extracellular Fluid Volume
• Intervention / Treatment: Drug: Albumin treatment

• Study Type: Interventional
• Enrollment (Anticipated): 52
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Anna Cruceta; Phone Number: 0034 93 2279838; Email: acruceta@clinic.ub.es

Study Locations

• Spain
  • Catalunya
    • Barcelona, Catalunya, Spain, 08036
      • Hospital Clínic de Barcelona
    • Barcelona, Catalunya, Spain
      • Hospital Moisés Broggi
    • Sabadell, Catalunya, Spain, 08208
      • Hospital Parc Tauli

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients included into the study must meet all the following criteria:

This study will include patients with liver cirrhosis and hypervolemic hyponatremia (serum sodium<130 mEq/L) admitted to hospital for any decompensation of the disease. Patients will be enrolled if hyponatremia persists after 3 days of diuretic withdrawal and fluid restriction. Women of child-bearing potential must have a negative pregnancy test in serum before the inclusion in the study and agree to use highly effective contraceptive methods, including intrauterine device, bilateral tubal occlusion or a vasectomized partner. Hormonal contraceptive methods will be avoided due to the risk of adverse events and impairment of liver function.

Exclusion Criteria:

1. Patients with Acute kidney injury 1B or higher;
2. Chronic kidney disease grade 3a or higher, defined as glomerular filtration rate <60ml/min for three months and markers of kidney damage (one or more): Albuminuria (Albumin excretion rate > 30 mg/24h; Albumin-to-creatinine ratio > 30 mg/g), Urine sediment abnormalities, Electrolyte and other abnormalities due to tubular disorders, Electrolyte and other abnormalities due to tubular disorders, Abnormalities detected by histology or Structural abnormalities detected by imaging.
3. Previous kidney or liver transplant;

4. Active infection apart from spontaneous bacterial peritonytis based on positive culture (blood, urine, sputum or other samples) or by the following criteria:

   1. Urinary infections: signs of systemic inflammation and more than 10 leukocytes per high-power field in urine;
   2. Pneumonia: compatible symptoms (cough, purulent sputum, chest pain, shortness of breath) and presence of new infiltrates on chest x-ray;
   3. Skin/soft tissue infection: physical exam findings of swelling, erythema, heat and tenderness in the skin;
   4. Acute cholangitis: signs of systemic inflammation1, compatible symptoms (right upper quadrant pain and jaundice) and radiological data of biliary obstruction, analytical data of cholestasis;
   5. Suspected bacterial infection: signs of systemic inflammation1 but no identifiable origin of this infection (polymorphonuclear cells in ascitic and pleural fluid < 250/mm3, normal urine sediment and chest Xray) After 48 hours of appropriate antibiotic treatment patients can be enrolled.
5. Spontaneous bacterial peritonitis.
6. Hypo or hyperthyroidism not controlled under adequate treatment.
7. Associated heart failure, defined as a New York Heart Association (NYHA) classification III or IV or heart failure with reduced ejection fraction (LVEF<40%). Previously known structural cardiomyopathy including ischemic cardiomyopathy, restrictive cardiomyopathy or valvular cardiomyopathy.
8. Hepatocellular carcinoma beyond Milan criteria.
9. Severe alcoholic hepatitis defined by Maddrey score ≥32 and/or MELD score ≥ 20
10. ACLF with two or more organ failures
11. Treatment with diuretics (furosemide or spironolactone), albumin infusion, somatostatin or terlipresin in the previous 3 days.
12. Symptomatic hyponatremia (manifested by cardio-respiratory distress, abnormal and deep somnolence, seizures or coma) with serum sodium below 120 mEq/L.
13. Previous known hypersensitivity to human albumin
14. Refuse to give informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: No treatment; No treatment.
Experimental: Albumin treatment; one dose per day of a 40g albumin g/l gram(s)/litre for 10 days.	Drug: Albumin treatment; one dose per day of a 40g albumin g/l gram(s)/litre for 10 days. resolution of hyponatremia, defined as an increase in serum sodium of more than 5 mEq/L with a final value > 130 mEq/L, maintained for at least 48 consecutive hours during the 10-day treatment period; Other Names: Human Albumin Grifols 200 g/l, solution for infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resolution of hyponatremia	defined as an increase in serum sodium of more than 5 mEq/L with a final value > 130 mEq/L	for at least 48 consecutive hours during the 10-day treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
partial resolution of hyponatremia	defined as an increase in serum sodium of more than 5meq/L with a final value below 130meq/L,	maintained for at least 48 consecutive hours during the 10-day treatment period.
Evaluation of systemic hemodynamics	mean arterial pressure	levels at day 0, at day 5 and at day 10 (or at the end of study in case of early termination due to primary endpoint reach from day 0 up to 10 days) of the study period.
kidney function	measurement of creatinine levels	levels at day 0, 5 and 10 (or at the end of study in case of early termination due to primary endpoint reach from day 0 up to 10 days).
Effects on the inflammatory profile	evaluation of PCR of plasma cytokines by using a multiplex kit including plasmatic cytokines related to immune response. This multiplex test will be performed at day 0 and day 10 of the study period (or at the end of study in case of early termination).	levels at day 0, and 10 (or at the end of study in case of early termination due to primary endpoint reach from day 0 up to 10 days).
Effects on neurocognitive function and quality	PHES questionnaire	levels at day 0, and 10 (or at the end of study in case of early termination due to primary endpoint reach from day 0 up to 10 days).
Effects on brain water content	performance of aMagnetic Resonance Spectroscopy (MRS)	levels at day 0, and 10 (or at the end of study in case of early termination due to primary endpoint reach from day 0 up to 10 days).
Effects of albumin administration on liver phagocytic capacity	Effects of albumin administration on liver phagocytic capacity as assessed by performance of hepatic SPECT with 99mTc-phytate at day 0 and 10 (or at the end of study in case of early termination).	levels at day 0, and 10 (or at the end of study in case of early termination due to primary endpoint reach from day 0 up to 10 days).
Effects on phagocytic capacity and inflammatory response of peripheral monocytes	Effects on phagocytic capacity and inflammatory response of peripheral monocytes will be assessed by performance specific tests (Phagotest and Phagoburst) evaluating the in vitro phagocytic capacity and burst response. Monocytes will be isolated and analysed at day 0 and at day 10 of the study period (or at the end of study in case of early termination).	levels at day 0, and 10 (or at the end of study in case of early termination due to primary endpoint reach from day 0 up to 10 days).
Effects of albumin administration of microbiome composition	Effects of albumin administration of microbiome composition as assessed by analysis of microbiome composition at day 0 and 10 of the study period (or at the end of study in case of early termination).	levels at day 0, and 10 (or at the end of study in case of early termination due to primary endpoint reach from day 0 up to 10 days).
Effects of albumin administration on development of infections, development of complications of cirrhosis and survival.	Effects of albumin administration on development of infections, development of complications of cirrhosis and survival.	levels at day 0, and 10 (or at the end of study in case of early termination due to primary endpoint reach from day 0 up to 10 days).
Effects of albumin administration on serum albumin levels	Effects of albumin administration on serum albumin levels assessed by measurement of mEq/L serum albumin levels at day 0, 5, 10, 28 and 90 of study period.	levels at day 0, 5, 10, 28 and 90 of study period.
evaluate treatment-related serious adverse events	To evaluate treatment-related serious adverse events during the treatment period	visit day 1,2,3,4,5,6,7,8,9,28 and 90

Collaborators and Investigators

• Sponsor: Fundacion Clinic per a la Recerca Biomédica

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2020
• Primary Completion (Anticipated): July 1, 2022
• Study Completion (Anticipated): November 1, 2022

Study Registration Dates

• First Submitted: March 28, 2019
• First Submitted That Met QC Criteria: May 6, 2019
• First Posted (Actual): May 8, 2019

Study Record Updates

• Last Update Posted (Actual): February 5, 2020
• Last Update Submitted That Met QC Criteria: February 4, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Metabolic Diseases; Liver Diseases; Water-Electrolyte Imbalance; Fibrosis; Liver Cirrhosis; Hyponatremia
• Other Study ID Numbers: 2019-000302-29

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No